Myology research highlights
RSS feedPYGM expression analysis in white blood cells: A complementary tool for diagnosing McArdle disease?
McArdle disease is caused by an inherited deficiency of the enzyme myophosphorylase, resulting in exercise intolerance from childhood and acute crises of early fatigue and contractures. In severe cases, these manifestations can be accompanied by rhabdomyolysis, myoglobinuria, and fatal renal failure. Diagnosis of McArdle disease is based on clinical diagnostic tests, together with an absence … [Read more]
Tubular aggregate myopathy resulting from dominant mutations in ORAI1
The store-operated Ca2+ release-activated Ca2+ (CRAC) channel is activated by diminished luminal Ca2+ levels in the endoplasmic reticulum and sarcoplasmic reticulum, and constitutes one of the major Ca2+ entry pathways in various tissues. Tubular aggregates are abnormal structures in the skeletal muscle, and although their mechanism of formation has not been clarified, altered Ca2+ homeostasis … [Read more]
Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy
Nemaline myopathy (NM) is a genetic muscle disorder characterized by muscle dysfunction and electron-dense protein accumulations (nemaline bodies) in myofibers. Pathogenic mutations have been described in 9 genes to date, but the genetic basis remains unknown in many cases. Here, using an approach that combined whole-exome sequencing (WES) and Sanger sequencing, the authors identified homozygous … [Read more]
Effect of antioxidants on FSHD muscle function
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by progressive weakness and atrophy of specific skeletal muscles. As growing evidence suggests that oxidative stress may contribute to FSHD pathology, antioxidants that might modulate or delay oxidative insults could help maintain FSHD muscle function. The main objective of this study was to test whether … [Read more]
Drisapersen DEMAND II study: Promising safety and efficacy results
Duchenne muscular dystrophy is caused by dystrophin deficiency and muscle deterioration and preferentially affects boys. Antisense-oligonucleotide-induced exon skipping allows synthesis of partially functional dystrophin. This exploratory, double-blind, placebo-controlled study investigated the efficacy and safety of drisapersen, a 2′-O-methyl-phosphorothioate antisense oligonucleotide, given for 48 weeks. Fifty three male patients (≥5 years of age; time to rise … [Read more]
Variants in the dystrophin gene are linked to cognitive function
This study investigated whether single-nucleotide dystrophin gene (DMD) variants are associated with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included … [Read more]
A new muscle glycogen storage disease associated with Glycogenin-1 deficiency
This study describes a slowly progressive myopathy in seven unrelated adult patients with storage of polyglucosan in muscle fibers. Genetic investigation revealed homozygous or compound heterozygous deleterious variants in the glycogenin-1 gene (GYG1). Most patients showed depletion of glycogenin-1 in skeletal muscle whereas one showed presence of glycogenin-1 lacking the C-terminal that normally binds glycogen … [Read more]
BIN1 mutations cause centronuclear myopathy
Centronuclear myopathies are congenital muscle disorders characterized by type I myofibre predominance and an increased number of muscle fibres with nuclear centralization. The severe neonatal X-linked form is due to mutations in MTM1, autosomal recessive centronuclear myopathy with neonatal or childhood onset results from mutations in BIN1 (amphiphysin 2), and dominant cases were previously associated … [Read more]
Clinical variability in FSHD due to epigenetic susceptibility
Facioscapulohumeral muscular dystrophy (FSHD: MIM#158900) is a common myopathy with marked but largely unexplained clinical inter- and intra-familial variability. FSHD is caused by contractions of the D4Z4 repeat array on chromosome 4 to 1-10 units (FSHD1), or by mutations in the D4Z4-binding chromatin modifier SMCHD1 (FSHD2). Both situations lead to a partial opening of the … [Read more]
Predictive markers of clinical outcome in the GRMD dog model of Duchenne Muscular Dystrophy
In the translational process of developing innovative therapies for DMD (Duchenne muscular dystrophy), the last pre-clinical validation step is often carried out in the most relevant animal model of this human disease namely the GRMD (Golden retriever muscular dystrophy) dog. GRMD dogs mimic the human disease, DMD, in many aspects including the inter-individual heterogeneity. This … [Read more]
